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Cited by 425

The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.

Transmembrane/cytoplasmic domain-mediated membrane type 1-matrix metalloprotease docking to invadopodia is required for cell invasion

Open access
Nakahara, Hirokazu, Howard, Linda, Thompson, Erik W., Sato, Hiroshi, Seiki, Motoharu, Yeh, Yunyun, Chen, Wen-Tien·1997·Proceedings of the National Academy of Sciences

Abstract

The invasion of human malignant melanoma cells into the extracellular matrix (ECM) involves the accumulation of proteases at sites of ECM degradation where activation of matrix metalloproteases (MMP) occurs. Here, we show that when membrane type 1 MMP (MT-MMP) was overexpressed in RPMI7951 human melanoma cells, the cells made contact with the ECM, activated soluble and ECM-bound MMP-2, and degraded and invaded the ECM. Further experiments demonstrated the importance of localization of the MT-MMP to invadopodia. Overexpression of MT-MMP without invadopodial localization caused activation of soluble MMP-2, but did not facilitate ECM degradation or cell invasiveness. Up-regulation of endogenous MT-MMP with concanavalin A caused activation of MMP-2. However, concanavalin A treatment prevented invadopodial localization of MT-MMP and ECM degradation. Neither a truncated MT-MMP mutant lacking transmembrane (TM) and cytoplasmic domains (ΔTM MT-MMP ), nor a chimeric MT-MMP containing the interleukin 2 receptor α chain (IL-2R) TM and cytoplasmic domains (ΔTM MT-MMP /TM IL-2R ) were localized to invadopodia or exhibited ECM degradation. Furthermore, a chimera of the TM/cytoplasmic domain of MT-MMP (TM MT-MMP ) with tissue inhibitor of MMP 1 (TIMP-1/TM MT-MMP ) directed the TIMP-1 molecule to invadopodia. Thus, the MT-MMP TM/cytoplasmic domain mediates the spatial organization of MT-MMP into invadopodia and subsequent degradation of the ECM.

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Metadata

Authors
Nakahara, H., Howard, L., Thompson, E. W., Sato, H., Seiki, M., Yeh, Y., & Chen, W.-T.
Venue
Proceedings of the National Academy of Sciences
Published
1997-07-22
Volume
94
Issue
15
Pages
7959-7964
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W89180169
Cited by
425
References
28
FWCI
9.76
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Transmembrane/cytoplasmic domain-mediated membrane type 1-matrix metalloprotease docking to invadopodia is required for cell invasion. https://app.cochat.ai/papers/10.1073/pnas.94.15.7959
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Nakahara, H., Howard, L., Thompson, E. W., Sato, H., Seiki, M., Yeh, Y., & Chen, W.-T. (1997). Transmembrane/cytoplasmic domain-mediated membrane type 1-matrix metalloprotease docking to invadopodia is required for cell invasion. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.94.15.7959

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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